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长链非编码RNA NR_027471作为miRNA - 8055的竞争性内源RNA,通过调控TP53INP1的表达来抑制骨肉瘤。

LncRNA NR_027471 Functions as a ceRNA for miRNA-8055 Leading to Suppression of Osteosarcoma by Regulating the Expression of TP53INP1.

作者信息

Chen Jiajia, Miao Wujun, Yang Saishuai, Yin Mengchen, Zhao Jianning, Song Dianwen

机构信息

Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, China.

Department of Orthopedics, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

出版信息

Front Oncol. 2020 Sep 29;10:563255. doi: 10.3389/fonc.2020.563255. eCollection 2020.

Abstract

Osteosarcoma is a malignancy with high aggressiveness and poor prognosis, which occurs mainly in children. The therapeutic strategy against osteosarcoma includes surgery combined with chemotherapy and radiotherapy. Although the treatment of osteosarcoma has been improved in recent years, there is a large proportion of patients with incurable osteosarcoma. Investigation of the mechanism of osteosarcoma progression would be of great help in discovering therapeutic targets for this disease. Long non-coding RNAs play critical roles in the pathogenesis of different types of cancer. The current study showed that long non-coding RNA NR_027471 was downregulated in osteosarcoma cells. and studies indicated that upregulation of NR_027471 impeded the viability, proliferation, and invasion of osteosarcoma, as well as induced cell cycle arrest at G1. In addition, binding of miR-8055 to NR_027471 was demonstrated, thereby influencing the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1). Knockdown of NR_027471 promoted epithelial-mesenchymal transition by inhibiting E-cadherin and increasing the expression of zinc finger E-box-binding homeobox 1 (ZEB1), Snail, and fibronectin. These results suggested that overexpression of NR_027471 upregulated TP53INP1 by sponging to miR-8055, leading to suppression of osteosarcoma cell proliferation and progression.

摘要

骨肉瘤是一种侵袭性高、预后差的恶性肿瘤,主要发生在儿童中。针对骨肉瘤的治疗策略包括手术联合化疗和放疗。尽管近年来骨肉瘤的治疗有所改善,但仍有很大一部分患者的骨肉瘤无法治愈。研究骨肉瘤进展的机制将有助于发现该疾病的治疗靶点。长链非编码RNA在不同类型癌症的发病机制中起着关键作用。目前的研究表明,长链非编码RNA NR_027471在骨肉瘤细胞中表达下调。 研究表明,NR_027471的上调会抑制骨肉瘤的活力、增殖和侵袭,并诱导细胞周期停滞在G1期。此外,还证实了miR-8055与NR_027471的结合,从而影响肿瘤蛋白p53诱导核蛋白1(TP53INP1)的表达。敲低NR_027471通过抑制E-钙黏蛋白并增加锌指E盒结合同源框1(ZEB1)、Snail和纤连蛋白的表达来促进上皮-间质转化。这些结果表明,NR_027471的过表达通过吸附miR-8055上调TP53INP1,从而抑制骨肉瘤细胞的增殖和进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd51/7550745/27ea03986fe8/fonc-10-563255-g0001.jpg

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